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1.
Front Immunol ; 12: 738093, 2021.
Article in English | MEDLINE | ID: covidwho-1518484

ABSTRACT

Disease caused by SARS-CoV-2 coronavirus (COVID-19) led to significant morbidity and mortality worldwide. A systemic hyper-inflammation characterizes severe COVID-19 disease, often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. Flow cytometry and next-generation sequencing were done on peripheral blood cells and urokinase-type plasminogen activator receptor (suPAR), and cytokines were measured from and mass spectrometry-based proteomics was done on plasma samples from an Indian cohort of COVID-19 patients. Publicly available single-cell RNA sequencing data were analyzed for validation of primary data. Statistical analyses were performed to validate risk stratification. We report here higher plasma abundance of suPAR, expressed by an abnormally expanded myeloid cell population, in severe COVID-19 patients with ARDS. The plasma suPAR level was found to be linked to a characteristic plasma proteome, associated with coagulation disorders and complement activation. Receiver operator characteristic curve analysis to predict mortality identified a cutoff value of suPAR at 1,996.809 pg/ml (odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower-than-cutoff suPAR levels were associated with a differential expression of the immune transcriptome as well as favorable clinical outcomes, in terms of both survival benefit (hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus, we identified suPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.


Subject(s)
COVID-19/blood , Receptors, Urokinase Plasminogen Activator/blood , SARS-CoV-2 , Adult , Aged , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/immunology , Blood Proteins/analysis , COVID-19/immunology , Cytokines/blood , Humans , Inflammation/blood , Inflammation/immunology , Middle Aged , Myeloid Cells/immunology , Proteome/analysis , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/immunology , Severity of Illness Index , Young Adult
2.
Indian J Med Res ; 151(2 & 3): 147-159, 2020.
Article in English | MEDLINE | ID: covidwho-32574

ABSTRACT

A novel coronavirus (nCoV) spillover event, with its epicenter in Wuhan, People's Republic of China, has emerged as a public health emergency of international concern. This began as an outbreak in December 2019, and till February 28, 2020, there have been 83,704 confirmed cases of novel coronavirus disease 2019 (COVID-19) globally, with 2,859 deaths, resulting in an overall case fatality rate of 3.41 per cent (95% confidence interval 3.29-3.54%). By this time (February 28, 2020) 58 countries or territories and one international conveyance (Diamond Princess Cruise Ship) were affected. As a part of the global response to manage and contain the pandemic, major emphasis was placed on generating research intelligence to guide evidence-based responses to contain the virus, which was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), owing to its genetic similarities with the SARS virus. This review summarizes the emerging evidence which can help guide the public health response, particularly in India. Key areas have been identified in which research needs to be conducted to generate critical intelligence for advising prevention and control efforts. The emergence of SARS-CoV-2 has once again exposed the weaknesses of global health systems preparedness, ability to respond to an infectious threat, the rapidity of transmission of infections across international borders and the ineffectiveness of knee-jerk policy responses to emerging/re-emerging infectious disease threats. The review concludes with the key learning points from the ongoing efforts to prevent and contain COVID-19 and identifies the need to invest in health systems, community-led response mechanisms and the need for preparedness and global health security.


Subject(s)
Coronavirus Infections/epidemiology , Delivery of Health Care/organization & administration , Pneumonia, Viral/epidemiology , Betacoronavirus , COVID-19 , Communicable Disease Control/organization & administration , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Humans , India , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Public Health , SARS-CoV-2
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